The proposed research will investigate the neuropsychological role of the subfornical organ, and in doing this, the neural control of water intake will also be studied. These studies will extend the discoveries of Simpson and Routtenberg (1972, 1973) showing that this structure 1) is a significant locus of cholinergic thirst, and 2) it appears to be a major dipsogenic site of action of the hormone, angiotensin-II. Intravascular angiotensin-induced drinking will be evaluated in animals with subfornical organ lesions and in animals in which a local competitive antagonist to angiotensin-II has been topically applied to the structure. In a dose response investigation the dipsogenic efficacy of all components of the renin-angiotensin system will be evaluated following intracranial chemical injection into the subfornical organ. Cholinergic nicotinic and muscarinic agonists and antagonists will be used to study the pharmacology of thirst induced by cholinergic agents acting on the subfornical organ. Finally, the interaction between angiotensin and cholinergic thirst will be evaluated pharmacologically in the subfornical organ, again with the method of intracranial chemical injection. The role of the subfornical organ in the control of water intake will thus be examined and information on the neurological-pharmacological nature of thirst will be provided. More complete understanding of the role of this brain structure, which may be crucial to mechanisms required for proper body fluid regulation, may lead to new insights into this essential behavioral process of thirst.